tbuckley/cabot-search huggingface dataset:
Abstract 15253: Mitochondrial Trifunctional Protein HADHA Regulates Mitochondrial Cardiolipin Content in Right Ventricle in Pulmonary Hypertension
Authors: Alexsandra Zimmer, Peng Zhang, Eric Wang, Emine Yalcin, Natalie D'Silva, Richard T Clements, Gaurav Choudhary
Journal: Circulation (2022)

Background: Pulmonary hypertension (PH) is prevalent in cardiopulmonary and metabolic diseases. Unmet energy needs due to mitochondrial (mito) dysfunction results in myocardial contractile failure, as seen in the dysfunctional right ventricles (RV). Cardiolipin (CL) is a critical lipid for mito structure and cristae organization that are essential for mito oxidative phosphorylation and ATP generation. The synthesis and maturation of CL involves many steps including a final step where acylation of monolysocardiolipin occurs and CL[18:1] 2 [18:2] 2 is converted to mature CL[18:2] 4 catalyzed by a mito trifunctional protein, HADHA. To date, the expression of mature CL and its regulation by HADHA in RV in PH remains unknown. Hypothesis: We hypothesize that HADHA regulates mito CL contents in RV in PH. Methods: Adult Sprague Dawley rats received 20 mg/kg sc SU5416 were exposed to 3 wks of hypoxia (10% FiO2), followed by 4 wks of normoxia. Control rats injected with vehicle were kept in normoxia. Hemodynamic and echocardiography were performed, followed by HADHA and CL analysis. We also generated in vitro models with H9c2 cells exposure in hypoxia and stable HADHA-knockdown H9c2 cells for mechanistic studies. Results: PH rats show RV dysfunction. Mito proteomics show a 70% decrease in HADHA expression in mito from RV of PH rats in comparison to the control rats, which is further validated by Western Blot and qPCR. Using mass spectrometry, mature CL (CL[18:2] 4 ) in RV of PH rats was found to decrease to 55% of that in RV of control rats (n=4-5/group, p &lt;0.05). Exposing the H9c2 cells to hypoxia (1% O 2 ) for 72 hrs recapitulate the downregulation of HADHA observed in the dysfunctional RV of PH rats, which is associated with a 70% reduction in the account of mature CL (n=6 each, p &lt;0.05). Importantly, adenoviral overexpression of HADHA almost brings the mature CL content in hypoxia to be comparable to cells in normoxia (n=6 each, p &lt;0.05). Our data also show that HADHA-specific knockdown is sufficient to decrease mature CL in H9c2 cells (Control 100% vs. HADHA Knockdown 33%, n=3 each, p &lt;0.05). Conclusions: Our data demonstrate that HADHA is critical in maintaining mature mito CL contents. Downregulation of HADHA contributes to reduced mito CL contents in RV in settings of PH.
Abstract 15275: Dysregulated Micro-RNA Expression in Fat Tissue Linked to Angiogenesis Response in Patients in Peripheral Artery Disease
Authors: Syed H Rizvi, Rosa Breton-Romero, Robert M Weisbrod, Naomi M Hamburg
Journal: Circulation (2022)

Microvascular dysfunction contributes to adverse clinical outcomes in patients with peripheral artery disease (PAD). Compromised angiogenesis may be a treatment target for limb ischemia but is challenging to assess in patients. Selected circulating miRNAs have been implicated in the pathogenesis of PAD, thus, we seek to identify and find correlation between altered miRNA signatures and angiogenesis potential in patients with PAD. We collected adipose tissue from ischemic limbs of patients with PAD (n=15, age=64±11, 33% women, 66% T2DM, 61% current smoking) at the time of revascularization surgery. Control adipose tissue was procured from patients without PAD undergoing joint replacement surgery (n=6, age=58±6, 50% women, 17% T2DM, 33% current smoking). Endothelial cell sprouting assay demonstrated lower angiogenesis response over 8 days in adipose tissue samples from PAD patients compared to controls (p=0.008). We performed miRNA profiling using NextSeq (Illumina Inc.) sequencer. miRNA NGS libraries were prepared using QIAseq miRNA Library Kit. Quality controlled NGS libraries were sequenced according to the manufacturer protocol. Our results demonstrated 40 upregulated and 11 downregulated miRNAs (FDR q&lt;0.01, log2 fold change&gt;2) in PAD fat tissue compared to controls. Using bioinformatics approaches to prioritize differentially expressed miRNA predicted to impact pathways relevant to cardiovascular disease, we identified miR205-5p and miR182-5p as top candidate. There were higher levels of miR205-5p (4.8-fold, FDRq=1.5e-10) and miR182-5p (4.1-fold, FDRq=5.4e-16) in adipose tissue from PAD patients compared to controls. We confirmed the differentially expressed levels using qPCR in selected samples. Ingenuity pathway analysis indicates that miR205-5p inhibits VEGF-A, a key regulator of angiogenesis. We observed a trend toward an association of miR205-5p (r=-0.58, p=0.1) and miR182-5p (r=-0.67, p=0.06) and lower angiogenesis response. Taken together our findings demonstrate impaired microvascular angiogenesis response in patients with PAD along with upregulation of selected miRNA predicted to impair angiogenesis pathways.
Abstract 15310: Impact of Peripheral Artery Disease on Outcomes in High-Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention
Authors: Rebecca M Cohen, Alessandro Spirito, Samantha Sartori, Clayton Snyder, Johny Nicolas, Birgit Vogel, Roja Thapi, Kayla Bedel-Franklin, Frans Beerkens, Davide Cao, Samin K Sharma, George Dangas, Annapoorna Kini, Roxana Mehran
Journal: Circulation (2022)

Introduction: Peripheral artery disease (PAD) has been shown to be related to worse outcomes after percutaneous coronary intervention (PCI). Little is known about the prognostic impact of PAD in patients with concomitant high bleeding risk (HBR) undergoing PCI. Hypothesis: The aim of this study was to assess ischemic and bleeding complications at 1 year after PCI in HBR patients with or without concomitant PAD. We hypothesized that in HBR patients with PAD, the risk of ischemic and, to a lesser extent, bleeding complications would be higher than in non-PAD patients. Methods: Consecutive patients undergoing PCI with drug-eluting stent implantation (DES) at a large tertiary-care center (Mount Sinai Hospital, New York, USA) between 2012 and 2019 and fulfilling the Academic Research Consortium HBR criteria were included. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI) and stroke 1 year after PCI. The key secondary outcome was major bleeding, according to a study specific definition. Results: Out of 7,192 HBR patients, 975 (13.6%) had concomitant PAD. Compared to non-PAD patients, PAD patients were more likely to have cardiovascular risk factors and comorbidities and to undergo a complex PCI. MACE occurred in 93 (11.4%) patients with PAD and 382 (7.3%) without PAD. The increased risk of MACE (HR 1.59, 95% CI 1.27-1.99, p&lt;0.001) was mainly driven by an excess of all-cause death and MI in PAD patients ( Figure 1 ). Bleeding was observed in 80 (8.5%) PAD and 410 (6.9%) non-PAD patients (HR 1.25, 95% CI 0.98-1.59, p=0.066). Conclusions: Among HBR patients undergoing PCI with DES implantation, PAD was associated with a higher risk of MACE and a borderline increase in bleeding events.
Abstract 15244: Rapid Recognition and Implementation of Mechanical Circulatory Support in Rare Fulminant Lymphocytic Myocarditis
Authors: Mohan Chandra Vinay Bharadwaj Gudiwada, Izza Saeed, Kathryn Kim
Journal: Circulation (2022)

Case Presentation: A 65 year-old woman with heart failure, nonischemic cardiomyopathy, atrial fibrillation, hypertension, prior stroke presented with chest pain and shortness of breath for three days. She was ill-appearing, hypotensive and tachypneic, with troponins reaching greater than 125,000 ng/L. Initial ECG demonstrated sinus rhythm with inferior ST elevations and lateral T wave inversions, however emergent catheterization revealed angiographically normal coronary arteries. Repeat 2D echocardiography showed sharp decline to ejection fraction (EF) 5-10%. Patient subsequently developed cardiogenic shock and despite inotropes, vasopressors and intra-aortic balloon pump, she suffered ventricular fibrillation arrest requiring defibrillation. This prompted escalation with emergent veno-arterial extracorporeal membrane oxygenation. Endomyocardial biopsy findings taken at that time were consistent with lymphocytic myocarditis with negative viral panel. Her hospital course was also complicated by acute renal injury, respiratory failure requiring intubation, metabolic acidosis and shock liver. With treatment with high dose steroids and mechanical circulatory support, the patient's severely diminished EF improved to 20% and she is undergoing placement of a left ventricular assist device. Discussion: Fulminant lymphocytic myocarditis is a rare disease that has clinically and pathologically distinct features from subacute or acute lymphocytic myocarditis particularly in its timeline of onset and features of hemodynamic compromise. It most frequently affects young and pediatric individuals and can result in significant mortality and morbidity. This case with an older patient with severe fulminant lymphocytic myocarditis confirmed on biopsy highlights: 1) the importance of early recognition affecting survival outcome, 2) golden standard for diagnosis with endomyocardial biopsy and immunohistochemical analysis for subtype-specific evidence-based treatment, and 3) integrated medical and surgical management, including mechanical circulatory support as an essential life-saving tool.
Abstract 15806: The Unique Cellular Ecosystem of the Human Basilic Vein: A Single-Cell Transcriptomic Analysis
Authors: Miguel G Rojas, Laisel Martinez, Simone Pereira-Simon, Zachary Zigmond, Nieves Santos Falcon, Alghidak Salama, Roberto I Vazquez-Padron
Journal: Circulation (2022)

Introduction: The cells in veins that contribute to vascular disease have not been fully characterized. This study generated a cellular atlas of the human basilic vein that will help understand vein physiology and pathologies. Methods: Single-cell sequencing of four basilic veins from healthy organ donors. Results: The integrated single-cell profile of 15,747 vein cells revealed 13 populations containing canonical and non-canonical vascular markers. The SMC population represented 16% of cells, of which 8% were purely contractile and the remaining 8% had a modulated phenotype. One cluster of modulated SMCs expressed ECM genes (collagen type IV, FN1, and TNC) while retaining high expression of contractile markers (DES, MYH11, ﻿ACTG2). The other SMC cluster had unique expression of CD36, APOE, LPL, and STEAP4, characteristic of lipid-processing cells. Surprisingly, these non-diseased veins contained a high number of resident immune cells, including pro-inflammatory macrophages (9%), CD163- and HMOX1-expressing Mhem-like macrophages (18%), lymphocytes (5%), and small counts of neutrophils (0.3%) and mast cells (0.7%). The adventitial cell populations highlighted the fundamental role of this layer in vascular maintenance, remodeling, and angiogenesis. We found a significant number of vasa vasorum ECs (6.5%) which differentiated from the luminal subpopulation (3.5%) by CD34, KDR, NOTCH4, and ICAM2 expression. There were also two types of fibroblasts. Classical fibroblasts (19%) had high expression of collagen genes, while adipogenic fibroblasts (21%) were characterized by high levels of ECM-interacting fibulins, adipocyte-associated genes (ADH1B, APOD, CXCL14, IGF1), and modulators of angiogenesis (ADM and EFEMP1). CellCall analyses identified 46 overrepresented ligand-receptor communication pathways in all clusters, including CXCL, FGF, IL-6, and complement signaling. Communication between pro-inflammatory macrophages and luminal ECs was the most overrepresented signaling connection. Conclusions: This comprehensive atlas of the human vein will help identify cell subpopulations relevant to venous pathologies, without relying on extrapolations from arterial biology and focusing instead on the uniqueness of vein tissues.
Abstract 15279: Ablation or Antiarrhythmic Drugs Alone in the Treatment of Ventricular Storm
Authors: Qiaonan Zhong, Abhishek Deshmukh, Courtney Bennett
Journal: Circulation (2022)

Introduction: Ventricular storms are managed with a combination of antiarrhythmic drugs (AAD) and ablation therapy. This study examines outcomes in patients who required cardiac intensive care unit (CICU) admission for ventricular storms. Methods: A retrospective cohort study was conducted of 200 random adult patients who admitted to the CICU at Mayo Clinic Rochester in 2016-2017 for ventricular storm. Continuous variables were analyzed with the Mann-Whitney U test. Categorical variables were analyzed with Fisher's exact test. Results: Of the 200 patients, 33 (16.5%) patients underwent ablation and AAD therapy for ventricular arrhythmias; 167 underwent AAD therapy alone. The patients in the ablation group were significantly younger (median of 60.3 vs. 72.7, U=1570, p&amp;lt;.001), had a lower Charlson Comorbidity Index (3.56 vs. 5.21, U=1916, p=.005), and a higher BMI (31.6 vs. 28.2, U=2028, p=.032). There was no difference in sex and race (white vs. non-white) between the two groups. The patients in the ablation groups had a significantly lower in-hospital mortality (0% vs. 20%, p=.001) and higher 1-year survival (91% vs. 63%, p=.001). There was no difference in length of stay in the CICU, length of stay in the hospital, or rate of hospital readmission within one year of discharge. Conclusions: Our study indicates that critically ill patients who undergo ablation and AAD for ventricular arrhythmias have decreased mortality compared to patients who underwent AAD therapy alone. More research is needed to elucidate whether this survival benefit is secondary to differences in treatment or baseline comorbidities in the two groups. Table 1: Characteristics and outcomes of patients undergoing ventricular storm treatment. Data is reported either as median or number of occurrences (%). Antiarrhythmic drug (AAD), Charlson Comorbidity Index (CCI), Body Mass Index (BMI), Cardiac Intensive Care Unit (CICU), Length of Stay in days (LOS). * Significance with p values &amp;lt; .05
Abstract 15287: Optimizing Guideline Directed Medical Therapy in Recently Hospitalized Patients With Heart Failure in a Large Urban Veterans Affairs Medical Center
Authors: Priyanka Moolchandani, SATYA PATEL, Ashley Saito, STEPHANIE GREGORIO, Jiwen Li
Journal: Circulation (2022)

Introduction: A quarter of patients hospitalized for heart failure either die or are re-hospitalized within 30 days. Optimization of guideline directed medical therapy (GDMT) has been shown to decrease both mortality and hospital readmissions. Methods: We used an existing heart failure clinical dashboard registry at our Veterans Affairs (VA) hospital to determine the rates of hospitalization from any medical cause and GDMT prescription rates from November to December 2022. We performed a retrospective chart review to validate dashboard results. Results: Twenty-nine patients in the registry were hospitalized within the last 30 days, with 5 patients excluded due to ongoing hospitalization; 19 were classified as heart failure with reduced ejection fraction (HFrEF, LVEF ≤ 40%), 4 as heart failure with preserved ejection fraction (LVEF ≥ 50%), and 2 unknown (no EF in 3 years). The rates of quadruple GDMT was 16% in all heart failure patients and 21% in patients with HFrEF (table 1). We performed a root cause analysis of low GDMT rates (figure 1). We used this data to secure buy-in from hospitalist medicine and cardiology to support a full-time cardiology pharmacist to screen all currently admitted patients with HFrEF. We created a standardized note template that gives recommendations for GDMT optimization prior to discharge. Conclusions: Although there is strong evidence that GDMT improves patient outcomes, many recently hospitalized patients are not optimized even after accounting for relative contraindications. We demonstrate that using tools such as a clinical dashboard and problem visualization with quality improvement methodology can both make GDMT optimization more tangible and also create buy-in from the health system to implement change.
Abstract 15330: Association of Cognition With Self-Care and With Health-Related Quality of Life in Heart Failure: Does Gender Moderate the Associations?
Authors: Miyeon Jung, Liana G Apostolova, Sujuan Gao, Debra K Moser, Irmina Gradus-Pizlo, Elham Algashgari, Suzanne Wang, Asa B Smith, Susan J Pressler
Journal: Circulation (2022)

Introduction: The associations of cognition with self-care of heart failure (HF) or with health-related quality of life (HRQL) have not been definitively established, Gender may moderate these associations. The aim of our study was to examine the associations between cognition and (1) HF self-care and (2) HRQL and explore (3) gender as a moderator. Methods: Baseline data were analyzed from a randomized trial of a cognitive intervention (N=73). A neuropsychological battery was used to assess cognition (i.e., global cognition, memory, attention, executive function, language). Self-Care of Heart Failure Index and Minnesota Living with Heart Failure were used to assess self-care (i.e., maintenance, management, perception, confidence) and HRQL, respectively. Moderated multiple regressions were performed using Hayes’ PROCESS macro v4.1 with cognition as the independent variable, gender as the moderator, and HF self-care or HRQL as dependent variables in separate models. Covariates were age and education. Results: Participants’ characteristics were: mean age=66±12 years; mean education=14±2 years; 56% women; mean LVEF=50±14%. Average scores were: self-care maintenance=68±12, management=64±16, perception=74±16, confidence=78±13, HRQL=29±22. Better attention scores were significantly associated with better self-care confidence (b=-1.002, p=.022). Gender moderated the relationships between attention and self-care perception (p=.030). Better attention was associated with better self-care perception among women but with worse self-care perception among men. Gender moderated the relationships between memory and HRQL (p=.050) as well as executive function and HRQL (p=.041). Women’s HRQL did not differ by memory or executive function, but men with better memory or executive function had better HRQL. Conclusion: Better attention was associated with better self-care confidence in HF. Associations between attention and self-care perception, memory and HRQL, and executive function and HRQL differed by gender. Interventions are needed to improve attention, memory, and executive function that may improve HF self-care and HRQL. The effects of gender need to be considered when designing future interventions.
Abstract 15267: LV Aneurysm Rupture - Dreaded Complication in an LVAD Patient
Authors: Noor Chima, Nicholas Luibil, Abdul H Azizi, Mandip S Gakhal, Carly Fabrizio
Journal: Circulation (2022)

Introduction: Left ventricular (LV) aneurysm rupture is a highly fatal mechanical complication, usually seen following a myocardial infarction. We describe a unique case of a patient with a left ventricular assist device (LVAD) who presented with cardiac arrest due to an LV aneurysm rupture. Case: A 57-year-old male with history of ischemic cardiomyopathy status post HeartMate3 (HM3) LVAD presented as an out of hospital cardiac arrest. Following resuscitation, Computed Tomography Angiography (CTA) of the chest showed a large long-standing aneurysm along the inferior wall of the LV measuring 2.9 x 3.3 x 3.5 cm with rupture dissecting the pericardium and extending to cause hemo-peritoneum (Figure1), not amenable to intervention. He had presented earlier in the month with anemia that stabilized with transfusion. Abdominal imaging at the time showed a contained bleed with unknown source. He had likely suffered a progressive bleed from the rupture leading to his cardiac arrest. Decision Making: Pseudoaneurysm has been reported as a rare complication with earlier generation LVADs, but to our knowledge, this is the first reported case of an aneurysm formation with rupture with an HM3 LVAD. Conclusions: With the advent of advanced mechanical support devices, there is a heightened need for awareness and cognizance of diagnosing such mechanical complications in this patient population. An early diagnosis requires a high clinical index of suspicion and a multi-disciplinary approach. Multimodality imaging including CT scan can assist with this diagnosis.
Abstract 250: Heart Rate And QRS Duration Predict Immediate Outcome In Pulseless Electrical Activity (PEA) During In-hospital Cardiac Arrest (IHCA)
Authors: Anders Norvik, Gunnar W. Skjeflo, Eirik Unneland, Daniel Bergum, David Buckler, Abhishek Bhardwaj, Trygve Eftestol, Elisabete Aramendi, Trond Nordseth, Benjamin Abella, Jan Terje Kvaloy, Eirik Skogvoll
Journal: Circulation (2022)

Introduction: PEA is commonly observed in in-hospital cardiac arrest. ROSC is currently the only indication of treatment response. Studies suggest that QRS duration (QRSd) and heart rate (HR) develop differently in patients who obtain ROSC or not. The aim of this study was to assess prospectively how QRSd and HR affect the immediate outcome of patients with PEA. Method: We investigated 327 episodes of IHCA in 298 patients, collected at two US and one Norwegian hospital. We assessed the ECG in 559 segments of PEA, measuring QRSd and HR in pauses of compressions, and noted the clinical state that followed PEA. We investigated the development of HR, QRSd, and transitions to ROSC or noROSC in a joint linear mixed/ time-to-event model, using software R version 4.0.3 with the package ‘JMbayes2’. Results: A HR increase by 50bpm increased the intensity (“hazard”) of gaining ROSC by 42% (p&lt;0.01), and a 50ms decrease in QRSd increased the intensity of gaining ROSC by 29% (p&lt;0.01). A decreasing HR had no significant impact; however, if QRSd increased by 50ms this increased the probability of transitioning to other lethal states (ventricular tachycardia or fibrillation, asystole, or death) by 24% (p&lt;0.01). Still, several patients experienced increasing QRSd before obtaining ROSC. The figure shows an example of how QRSd (lower left) and HR (upper left) developed in one PEA segment overlaid the linear model (blue line). The estimated probability of obtaining ROSC (green line with 95% CI) or transitioning to other arrest states (red line) over the next 4 minutes are displayed to the right. This patient obtained ROSC at approx. 7min. Conclusion: HR and QRSd conveys information of the immediate outcome (ROSC/noROSC) in PEA. This may guide the team in their efforts, and possibly allow for individual tailoring of treatment, e.g., by delaying a (potentially harmful) epinephrine administration. Due to low specificity, the model cannot support termination of resuscitation.